From R-CHOP to revolution: How CAR T-Cells, ADCs, and bispecific antibodies are transforming DLBCL treatment

Diffuse large B-cell lymphoma (DLBCL) is the most common and aggressive subtype of non-Hodgkin lymphoma, with R-CHOP as the standard first-line treatment. However, many patients experience relapse or refractory disease, prompting the need for new therapeutic approaches. Recent advances, including chimeric antigen receptor (CAR) T-cell therapies, antibody-drug conjugates (ADCs), bispecific antibodies (bsAbs), immunomodulators, and Exportin-1 (XPO-1) inhibitors have transformed treatment strategies.

A comprehensive literature review was conducted using PubMed up to January 2025. Boolean operators and MeSH terms "Lymphoma", "Large-B-cell" and "Diffuse" along with DLBCL-related keywords, were utilized following thorough examination of existing literature.

CAR T-cell therapies, and particularly axicabtagene ciloleucel and lisocabtagene maraleucel, demonstrated superior event-free survival and overall survival. ADCs, such as polatuzumab vedotin, improved PFS with a manageable toxicity profile, while bsAbs like glofitamab and epcoritamab showed high response rates in relapsed or refractory DLBCL. Major toxicities from these new treatments include cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS).

Novel therapies have significantly improved DLBCL outcomes, however challenges remain, including treatment toxicity, accessibility, and variability in patients' response. Future research should aim to optimize combination therapies, identify biomarkers predictive of response, and enhance toxicity management to improve patient care.